Inhaled galectin-3 inhibitor shows promise for COVID-19 pneumonitis
An inhaled potent thiodigalactoside galectin-3 inhibitor appeared well-tolerated among patients with COVID-19 pneumonitis, according to study results published in American Journal of Respiratory and Critical Care Medicine.
Prior to being tested among patients with COVID-19 pneumonitis, a previous study showed inhaled GB0139 (Galecto Biotech) reduced plasma biomarkers related to the progression of idiopathic pulmonary fibrosis (IPF), according to researchers.
“High circulating galectin-3 is associated with poor outcomes in patients with coronavirus disease (COVID-19),” Erin E. Gaughan, of the Centre for Inflammation Research at Edinburgh BioQuarter, and colleagues wrote. “We hypothesized that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with anti-inflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis.”
Safety for COVID-19 pneumonitis treatment
In DEFINE, a phase Ib/IIa randomized controlled clinical trial, Gaughan and colleagues assessed 41 patients hospitalized with COVID-19 pneumonitis to determine the safety and tolerability of inhaled GB0139 in this patient population. In addition, researchers evaluated pharmacokinetic and pharmacodynamic properties of the therapy as secondary outcomes.
In addition to receiving standard of care, researchers randomly assigned 20 patients (mean age, 65.2 years; 55% men) to also receive 10 mg inhaled GB0139 two times a day for 48 hours, then one time a day for 14 days or until discharge, whereas the other 21 patients (mean age, 65 years; 57.1% men) received standard of care alone.
Both groups of patients experienced a similar number of adverse events, at 40 events total in the GB0139 group and 35 in the standard-of-care group, with a comparable proportion of patients in each group experiencing any adverse event (70% vs. 57.1%). One patient in the treatment group experienced any serious adverse event — including small bowel obstruction, paracetamol overdose and worsening hyponatremia, all of which were considered unrelated to treatment — compared with none in the standard-of-care group.
Five patients who received GB0139 reported mildly severe adverse events that researchers believed could be linked to the inhaled drug, including an isolated instance of prolonged corrected QT interval on ECG with no arrhythmia that spontaneously resolved, nausea, sore throat, oral thrush and hair loss. However, researchers wrote that none of these adverse reactions have been noted before in more than 400 patients with IPF who have taken GB0139.
None of the four deaths in the patient group receiving GB0139 were deemed related to the drug.
Secondary outcomes, biomarkers
In terms of secondary outcomes, researchers observed plasma GB0139 in all patients after exposure, with a post-hoc analysis of mean serum concentration of galectin-3 over days 2 to 7 showing significant decreases compared with the standard-of-care group (P = .0099).
Regarding inflammation biomarkers, a post-hoc analysis showed that the GB0139 group had greater rates of decline than the standard-of-care group in C-reactive protein, lactate dehydrogenase and neutrophil to lymphocyte ratio, and CXCL10.
Also, the treatment group also had consistently low concentrations of D-dimer, a larger rate of decline in plasma concentrations of fibrinogen/platelet ratio and an increase in platelet count, according to researchers. Patients receiving GB0139 also showed lower concentrations of YKL-40, a biomarker of fibrosis.
However, patients in the standard-of-care group had more oxygen-free days than the GB0139 group (29/86 vs. 19/123; rate ratio = 0.45; 95% highest posterior density credible interval, 0.25-0.82).
“Despite a small sample size, this study adds further weight to the therapeutic potential of galectin-3 inhibition in the treatment of patients with COVID-19,” Gaughan and colleagues wrote. “Although the trial was not powered to assess efficacy, GB0139 treatment showed a greater decrease in the rate of inflammatory and physiological biomarkers associated with COVID-19 severity in patients on GB0139 plus standard of care compared with standard of care.”
Applicability of results
This study by Gaughan and colleagues presents important data on an inhaled drug that could help patients with COVID-19 pneumonitis, but one limitation is that most patients had a low level of illness severity, according to an accompanying editorial by Kiran Reddy, MB, of the school of medicine, dentistry and biomedical sciences at Queen’s University Belfast, and colleagues.
“The biomarker data in the DEFINE trial suggest that GB0139 may attenuate inflammation, coagulopathy, and fibrosis in COVID-19,” Reddy and colleagues wrote. “However, this is a small study population, and results should be interpreted cautiously. In addition, some results were observed only in the subset of patients with a National Early Warning Score 2 (NEWS2) score greater than 4, which may further increase the risk of bias due to the smaller sample size and amplified effect of outliers.”